1. Field of the Invention
The present invention relates to topical anesthetics. More particularly, the present invention relates to topical anesthetics for lacerations.
2. General Background of the Invention
There has been a long-felt need for a topical anesthetic that affords painless, safe application, does not contain narcotics or controlled substances, and has a maximum safety with complete anesthesia.
The topical anesthetic TAC (tetracaine, adrenaline, cocaine) was introduced by Pryor et al. in 1980. It was a revolutionary new approach to laceration repair (1) (the numbers in parentheses refer to the numbers of the articles cited in the Appendix--all of these articles are hereby incorporated by reference). However, there have been varying reports of its efficacy, safety, side effects, and wound infection rates.
Several studies since that of Pryor et al. have shown varying efficacy of the TAC solution, and have compared the efficacy of TAC to injected lidocaine in application and anesthetic properties (2-5).
TAC's effectiveness and acceptance as an adequate topical anesthetic for laceration repair has been demonstrated in pediatric patients in several studies. TAC was found to be effective in lacerations by Bonadio, (4) and provided adequate anesthesia and was better received by patients in comparison to injected lidocaine according to Hegenbarth (3) and Anderson (2). Bonadio demonstrated good results with use of a cocaine-adrenaline gel in pediatric patients (21).
Recent studies have demonstrated increased risks with the use of TAC solutions. Seizures and even death, presumably secondary to absorption of the cocaine component of TAC, have been reported (6,7,8). Animal studies and clinical human trials have demonstrated presence of cocaine and metabolites in urine (9,10) and blood (11,12) after use of TAC solution for laceration repair in a substantial number of patients. Another theoretical risk has been the higher incidence of local wound complications seen in animal studies (13,14), but this has not been borne out in clinical studies.
To address the toxic side effects of TAC, several recent studies have attempted to compare altered formulations of the components. These alterations include decreasing the amount of cocaine (15,16), using TAC with and without cocaine (17), cocaine alone, (18) tetracaine alone, (19) or eliminating the tetracaine component (20,21). None of these formulations were more effective than TAC, and most were not as effective (especially when cocaine was omitted).
Previous studies of topical anesthetics for laceration repair began to appear in 1980 when Pryor et al. introduced TAC. TAC, applied as a topical anesthetic, was found to be equal to injected lidocaine in all locations for anesthetic efficacy and better accepted by patients and families (1). Some subsequent studies have shown TAC (applied topically) to be as effective as injected lidocaine in all locations (2,5) while other studies have shown TAC to be effective only on the face and scalp (3,4,19).
Particular reference has been made to pediatric patients in several studies. A topically applied anesthetic that is painless to apply and effective is desirable in this patient population in particular (2,3,4).
Studies of the infections associated with TAC use began to appear in 1982. In his animal study Barker reported TAC-treated wounds had increased infection rates, necrosis, and higher bacterial counts compared to control wounds (13). In 1990, however, Martin et al. reported that in contaminated porcine wounds TAC did not cause an increase in bacterial proliferation compared to lidocaine infiltration (14). Generally, clinical studies comparing TAC versus lidocaine have not shown greater infection rates in TAC treated wounds (1-5,15,17-19).
Other problems associated with TAC use began to appear in the literature. Mucous membrane absorption may result in hyperexcitability, euphoria, tachcardia, hypertension, and seizures (6). Seizures have been reported with application to burns (29). Dripping into the eyes has been reported with resultant corneal abrasions (30,31). Two deaths have been reported secondary to TAC application close to mucous membranes. One case was a seven month old who had TAC applied twice with dripping into the mouth and nose (8). The other was a four year old with application directly to the tongue (32). These problems are likely to be due to absorption of components of TAC solution. Animal and clinical studies of urine and plasma levels of components of TAC have demonstrated positive cocaine and metabolite levels. Interestingly, tetracaine levels were not measurable in any of these studies (9,11,12).
Because of problems associated with TAC absorption, especially to mucous membranes, several studies have attempted to change the formulation of TAC to make it potentially less toxic without affecting the anesthetic ability. Prior attempts at altering TAC to improve its efficacy have compared TAC to solutions with either differing concentrations of all of the components of TAC or solutions of one or two of the components. Schaffer compared TAC with and without cocaine and concluded cocaine provided a significant proportion of the anesthetic property of TAC (17). In a previous study of TAC versus cocaine alone, the cocaine solution did not work as well as the TAC solution (18). Others have shown that tetracaine alone is not effective (19, 33). Smith et al. compared three different formulations of tetracaine, adrenaline and cocaine and found a 4% cocaine solution worked as well as a 7% or 11.8% solution (15). Bonadio and Wagner showed that when they halved the amount of cocaine in the TAC solution, it still worked effectively (16) and that cocaine adrenaline (CA) was as effective as TAC. They recommended removal of the tetracaine component (20). A gel form of CA was also introduced by Bonadio and found to be effective in a non-randomized non-blinded study and perhaps may require less solution for effective anesthesia (21). Removal of the controlled substance component (cocaine), which appears to be the major cause of TAC-associated toxicity, has never been possible without loss of efficacy of the solution (17, 19).
Topical lidocaine and tetracaine have both been used safely on mucous membranes in the past (33-36). Thrasher et al. recommend topical lidocaine use for bladder biopsy, (33) Rowbother and Fields recommend its use for herpetic neuralgia, (34) and Borfeldt et al. recommend it for burns (35). In studies by Adriani and Zepenick tetracaine was found to be one of the most effective and longest lasting topical anesthetics (more effective than cocaine or lidocaine) (37). Tetracaine has been used in topical application for many years in endoscopic procedures (38) and recently for insertion of intravenous catheters in intact skin (39). It has been a part of the TAC mixture since its introduction by Pryor et al. (1).
Toxicity related to lidocaine and tetracaine have in the past involved mucous membrane application with large concentrations applied or ingested. Seizures were caused in an infant ingesting 80 cc viscous lidocaine over an undetermined time period (40) and in an eleven month old being treated for teething pain (41) and in a two year old who drank viscous lidocaine in error (42). Adriani et al. reported a large series of tetracaine fatalities when used topically on mucous membranes for endoscopic procedures. However in most instances more than 160 mg were used (43).